A Randomized, Controlled Trial Comparing the Safety and Efficacy of Luspatercept Plus Cyclosporine Versus Cyclosporine Alone for the Treatment of Newly Diagnosed Non-transfusion-dependent Non-severe Aplastic Anemia (NSAA)
试验速览
- 阶段
- 4 期
- 状态
- 撤回
- 入组人数
- 58
- 试验地点
- 1
- 主要终点
- overall response rate (ORR)
研究概览
简要总结
In a randomized, controlled clinical trial, the efficacy and safety of rodsipil combined with cyclosporine versus cyclosporine alone in the treatment of newly diagnosed non-transfusion-dependent NSAA were compared.
详细描述
Conduct a comparative evaluation of the effectiveness and safety of Luspatercept combined with cyclosporine versus cyclosporine monotherapy in the treatment of newly diagnosed non-transfusion-dependent non-severe aplastic anemia (NSAA). Patients were randomized in a 1:1 ratio and assigned to one of two groups: Group A, Luspatercept combined with cyclosporine: received Luspatercept (1.0 mg/kg, subcutaneous injection every 3 weeks), cyclosporine (3-5mg/kg/day), adjusted based on hematological parameters, for at least 6 months to assess efficacy. Effective patients continued to receive cyclosporine treatment for at least 1.5 years, with a gradual reduction in dosage; Group B, cyclosporine: received 3-5mg/kg/day, adjusted based on hematological parameters, for at least 6 months to assess efficacy, with effective patients continuing to receive cyclosporine treatment for at least 1.5 years, with a gradual reduction in dosage. Hgb below 60g/L was allowed, or in emergency conditions, blood transfusion was allowed. Platelets below 20×10^9/L or with obvious bleeding tendency were allowed to receive platelet transfusion. If neutrophil count was below 1.0×10^9/L, G-CSF was allowed until neutrophil count recovered to above 1.0×10^9/L. Symptoms, treatment-related adverse events, signs, blood transfusion volume, and laboratory tests (including reticulocyte count) were recorded at least every 3 months for the first 3 months, and every 6 months thereafter until 6 months, and bone marrow aspiration, biopsy, and chromosome examination were performed at least every 6 months to observe efficacy and safety.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years
- •Hemoglobin level of 6-10 g/dL
- •Definition of NSAA: Patients with AA diagnosis but not SAA or VSAA diagnosis (at least two of the following conditions can be diagnosed as AA: (i) Hemoglobin < 100 g/L; (ii) Platelet count < 50×10^9/L; (iii) Neutrophil count < 1.5×10^9/L. SAA diagnosis criteria include less than 25% (or 25-50%, but residual hematopoietic cells < 30%) of bone marrow cells, plus at least two of the following conditions: (i) Neutrophil count < 0.5×10^9/L; (ii) Platelet count < 20×10^9/L; (iii) Retroperitoneal lymph node count < 20×10^9/L. VSAA meets the criteria for SAA, but with neutrophil count < 0.2×10^9/L. (British guidelines, 2015))
- •No active infection
- •No other concurrent neoplasms (except in situ carcinoma)
- •Baseline liver and renal function within 1.5 times of normal value
- •No pregnancy or breastfeeding
- •Agree to sign informed consent form
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
排除标准
- •Congenital aplastic anemia
- •Presence of chromosomal aberrations
- •Cytogenetic evidence of clonal hematological myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML)
- •PNH clone ≥50%
- •Previous use of alemtuzumab, any ATG, or any dose of cyclosporine for immunosuppressive treatment
- •Previous hematopoietic stem cell transplant (HSCT)
- •Uncontrolled infection or bleeding under standard treatment
- •Allergy to rituximab, cyclosporine, or excipients
- •History of allergy to polyethylene glycol (PEG) 80
- •Active infection or cirrhosis of the liver or portal hypertension due to HIV, HCV, or HBV
- •Screening QTcF (Fridericia QT corrected formula) less than 450 milliseconds or less than 480 milliseconds of bundle branch block determined by three ECG averages, and assessed on-site; unstable angina; uncontrolled hypertension (>180/100 mmHg); pulmonary hypertension
- •Any malignant tumor within 5 years, except local basal cell carcinoma; previous thromboembolic event, history of myocardial infarction or stroke (including antiphospholipid syndrome); currently using anticoagulants
- •Pregnant or lactating women
- •Participated in another clinical trial within 3 months
研究组 & 干预措施
Luspatercept combined with cyclosporine
Administered Luspatercept (1.0 mg/kg, subcutaneous injection every 3 weeks), and Cyclosporine (3-5mg/kg/day) adjusted according to hematological parameters, for at least 6 months to evaluate efficacy. Effective patients will continue to receive Cyclosporine treatment for at least 1.5 years, followed by a gradual reduction in dosage.
干预措施: Luspatercept (Drug)
Luspatercept combined with cyclosporine
Administered Luspatercept (1.0 mg/kg, subcutaneous injection every 3 weeks), and Cyclosporine (3-5mg/kg/day) adjusted according to hematological parameters, for at least 6 months to evaluate efficacy. Effective patients will continue to receive Cyclosporine treatment for at least 1.5 years, followed by a gradual reduction in dosage.
干预措施: cyclosporine (Drug)
cyclosporine
Give cyclosporine 3-5mg/kg/day, adjust the dose based on the blood count, and administer it for at least 6 months to evaluate the efficacy. If effective, the patient will continue to receive cyclosporine treatment for at least 1.5 years, followed by a gradual reduction in dosage.
干预措施: cyclosporine (Drug)
结局指标
主要结局
overall response rate (ORR)
时间窗: 6 month
Proportion of patients who achieved complete response, partial response and hematological response
次要结局
- overall response rate (ORR)(12 month)
- adverse event rate(12 month)
研究者
Bing Han
Professor
Peking Union Medical College Hospital